A research review by scientists at British American Tobacco suggests that the regulatory functions and inherent stability of microRNAs make them suitable biomarker candidates for early detection of the molecular and genetic changes associated with smoking-related diseases (Biomarkers Med. (2012) 6(5), 671–684).

‘MicroRNAs (miRNAs) are non-coding RNA molecules that play key roles in regulating gene expression,’ according to a BAT press note issued yesterday. ‘They are involved in a wide range of biological processes such as cell cycle control, apoptosis and several developmental and physiological processes.

‘Chronic cigarette smoke causes various molecular and genetic changes in the respiratory tract and is a high risk factor for such smoking-related diseases as lung cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease.

‘The potential of miRNAs as effective biomarkers of biological effect is borne out by the results of several studies demonstrating that miRNA expression patterns differ in diseased and normal tissue. miRNAs also play a vital role in inflammation, which contributes to development of these diseases, and serve as key regulators of immune response.

‘It is cancer in particular in which miRNAs have so far shown the most promise as biomarkers. Some miRNAs act as oncogenes, some play important roles in tumour invasion and metastasis, while others suppress tumours.

‘Research shows that cigarette smoke impairs the regulatory function of a variety of miRNAs in all stages of lung cancer formation, but that resulting changes in miRNA expression only become irreversible after exposure to high doses of smoke for some time.’

Changes in miRNA expression can indicate not only the presence of a tumour but also its origin and stage of development. “By measuring miRNAs in several types of body fluids, it is possible to robustly discriminate between patients with disease and healthy controls, and reliably identify patients with good from poor prognosis,” said chief scientific officer, Dr. Chris Proctor. “Additionally, miRNA expression changes are identified at early stages of disease development. Therefore the potential of miRNAs as biomarkers of biological effect appears extremely promising.”

In addition, miRNAs – unlike messenger RNAs (mRNAs) – are highly stable in tissue and blood, are resistant to RNA degradation, and can be found in blood, saliva and urine, enabling easy, non-invasive detection.

“The changing profile of miRNA expression in diseased and normal tissues, the dysregulation of a variety of miRNAs throughout all stages of pulmonary carcinogenesis by cigarette smoke, non-invasive sampling methods and the reversibility of miRNA expression on smoking cessation reported indicate the relevance of miRNAs as potentially ideal biomarkers of biological effect,” said the review author, BAT’s Anisha Banerjee.

The researchers note that further studies are required to identify the miRNAs most relevant to specific diseases and to develop robust isolation and detection methods.